Grant: Operating Grant

There are currently no treatments that promote substantial functional recovery following a persons spinal cord injury (SCI). However, findings of adaptive changes, in other words, plasticity, in the adult nervous system are beginning to offer new avenues of potential treatment. In an animal model of SCI, we have demonstrated that plasticity can be amplified by rehabilitative training, provided that it begins early after an injury. Moreover, we recently found that training success decreases following injury in association with a decline of the level of intracellular messenger molecule, cyclic AMP, in the brain. This intriguing finding forms the basis for the current proposal. We know that cyclic AMP strongly influences various intracellular processes, including the ability of neurons to grow. Therefore, we will examine whether the post injury decrease in cyclic AMP interferes with the training-induced plasticity, which could explain the progressive decrease in training efficacy. We plan, with this experiment, to determine whether we can establish a causal relationship between the decline in training efficacy on functional recovery over the weeks following injury and the decline in cAMP levels. We also have a secondary purpose: We want to demonstrate that the decline of cortical cAMP levels is caused by neuronal inactivity and is not a direct consequence of the injury to the nerve cells. We will explore a pharmacological increase of cAMP in combination with training in rats with chronic SCI. These would, we believe, open the door for new treatment approaches. In summary, we will investigate the reason for the progressive decline of rehabilitation training efficacy following spinal cord injuries and offer new treatment approaches to enhance training effects.